1. Field of the Invention
This invention relates to an apparatus for promoting a reaction between solid and liquid phases. The apparatus is used to insure that an efficient reaction takes place between a solid-phase reactive substance that is bound to the inside surface of a tubular reaction vessel and a reactive substance that exists in the liquid phase in the reaction vessel. More particularly, this invention relates to an apparatus for promoting a reaction between solid and liquid phases that is suitable for use in promoting various reactions including immunoreactions, enzymatic reactions and reactions using DNA probes.
2. Description of the Prior Art
Immunoassay techniques utilizing such reactions as antigen-antibody reactions are currently employed as a means of measuring concentration of substances that are present in very small amounts in body fluids such as urine, blood serum, blood plasma and the like, and concentration of drugs administered to a living body in the body fluids.
These reactions can conveniently be carried out by using the inside surface of reaction vessels as a carrier for immobilizing and insolubilizing antibodies, antigens and other reactive substances. For example, plastic test tubes are easy to handle and used with preference since they serve both as a carrier for immobilizing a reactive substance and as a reaction vessel. Reactions in vessels having a reactive substance immobilized or insolubilized on their inner wall are conventionally carried out by a stationary process in which the reaction vessel such as a test tube is allowed to stand in an upright position for the reaction to take place therein. However, in this stationary process, the area of the inside surface (the inner wall) of the reaction vessel that can be utilized for the reaction is limited by the volume of the sample solution in the vessel and the amount of the aforementioned reactive substance that can be bound to said inside surface is also limited by the available surface area. Thus, the amount of the aforementioned reactive substance relative to the sample solution cannot be increased as much as other conventional carriers used in the stationary method such as plastic beads, filter paper and fine cellulosic particles and this had led to an unduly prolonged reaction time.
With a view to overcoming these disadvantages, the applicant of the present invention has already proposed an apparatus capable of permitting the intended reaction to be fully carried out within a short period of time by an inclined rotational method wherein the reaction vessel is rotated with its own longitudinal axis inclined at a predetermined angle from horizontal direction. Japanese Patent Publication Kokoku No. 61-61857 discloses a process wherein the inclined reaction vessel is simultaneously rotated around its own longitudinal axis with the axis inclined at a predetermined angle from the horizontal direction and transported in horizontal direction to automatically control the reaction time, as well as an apparatus used for carrying out said process. Japanese Patent Application Kokai No. 58-61469 discloses an apparatus wherein the inclined reaction vessel is not only rotated around its own longitudinal axis but also revolved around another axis parallel to the longitudinal axis of the reaction vessel to achieve transporting and automatically control the reaction time. The key concept of these apparatuses is that if an inclined reaction vessel is allowed to rotate about its own axis, the liquid phase in the vessel is moved in contact with a wide area of its inside surface to promote the reaction taking place within the vessel, and the intended effect can be attained by this approach.
Further, the reaction apparatuses described in the aforementioned prior patents are so designed that the reaction vessel is to be loaded manually on the apparatus and no teaching whatsoever is made of an apparatus in which the reaction vessel can be automatically loaded.
Under these circumstances, this applicant proposed in Japanese Patent Application Kokai Nos. 61-114731 and 61-114732 an apparatus in which the aforementioned reaction vessel is raised from an inclined position in which it is allowed to rotate about its own axis to an upright position. This erecting apparatus serves to hold the reaction vessel in an upright position so that in various immunoassay procedures, particularly in reaction procedures, a step such as washing that precedes or follows the step in which the reaction vessel is rotated in an inclined state in order to promote the reaction can be performed in an easy and advantageous manner.
The above-described apparatuses proposed by the applicant for carrying out the reaction between a solid and a liquid phase are capable of achieving the intended promotion of the reaction of interest. However, each of the reaction vessels employed has to be rotated about its own axis and this increases not only the structural complexity but also the cost of the reaction apparatus. Further, the procedures involved in loading and unloading the individual reaction vessels from the apparatus are extremely cumbersome and complicated.
The reaction apparatus proposed in Japanese Patent Publication Kokoku No. 61-61857, supra, creates the force of rotating the reaction vessels by the friction between the holder or belt and each reaction vessel. This is also true with the reaction apparatus proposed in Japanese Patent Application KOKAI No. 58-61469, supra which creates the force of rotating the vessel supporting holder by the friction between said vessel supporting holder and the rotating disk which is driven by a motor. Accordingly, if the outside surface (the outer wall) of a certain reaction vessel is wetted accidentally with the liquid content or water, or if the environment of use is such that the moisture in the surrounding atmosphere condenses to collect on said outside surface of that reaction vessel, there occurs an abrupt drop in the effective frictional force and the failure to achieve the necessary rotation during the predetermined reaction time can lead to inexact measurements. Thus, it has been difficult in the case of power transmission with friction to insure that no slippage will occur under any conditions. On the other hand, the reaction conditions must be made uniform in measurements, particularly in immunoassays which make use of immunological reactions, and yet prior art reaction apparatuses described above will often fail to insure completely identical reaction conditions (especially, agitating or mixing conditions, the rotational speed and the number of rotations of each reaction vessel) in all reaction vessels (spinning conditions).
In addition, the procedures involved in loading and unloading the individual reaction vessels from the apparatus have been extremely cumbersome and complicated.
Further, in order to insure identical conditions of the reaction that takes place in many reaction vessels and to enable even unskilled operators to achieve the intended measurement under the same conditions, the reaction apparatus is preferably designed in such a way that the individual reaction vessels can be loaded and unloaded automatically to realize automated measurements. However, none of the existing reaction apparatuses are adapted to permit the reaction vessels to be loaded and unloaded in a simple and automatic way. The erecting apparatuses described in Japanese Patent Application KOKAI Nos. 61-114731 and 61-114732, supra, are not designed so that the reaction vessels are loaded in their associated loading positions in a pinched state and, as a result, the force exerted upon the reaction vessels during their loading is not uniform enough to insure smooth loading and this can cause either spillage of the liquid content or accidental breaking of the vessels. The failure to load or unload reaction vessels in a safe, correct and reliable manner has been particularly common in such cases as where vessel securing means are employed.